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Corticotropin-releasing Hormone (corticotropin-releasing + hormone)
Selected AbstractsFunctional expression of corticotropin-releasing hormone (CRH) receptor 1 in cultured rat microgliaJOURNAL OF NEUROCHEMISTRY, Issue 2 2002Wei Wang Abstract Corticotropin-releasing hormone (CRH), known as a key regulator of the hypothalamic,pituitary,adrenal axis response to stress, elicits its biological effects by binding to two membrane receptors (CRH-R1 and CRH-R2). The present studies examined the presence of functional expression of CRH receptors in cultured microglia of rat. CRH-R1 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR), western blotting and receptor chemical cross-linking assay in cultured microglia. CRH-R2 mRNA was undectable by RT-PCR. The radioligand binding analysis using [125I]Tyr-rat/human CRH revealed a high affinity binding site (Kd of 1.2 nm and Bmax of 84 fmol/mg of protein). Competition studies using CRH and related peptides indicated kinetic and pharmacological characteristics consistent with the CRH-R1 receptor subtype. Receptor chemical cross-linking assay demonstrated a single band of CRH receptor with a molecular weight of ,77 kDa, which was inhibited in the presence of excess unlabeled rat/human CRH in a dose-dependent manner and inhibited by a CRH receptor,antagonist astressin. Functional coupled cAMP production in cultured microglia was stimulated by exogenous addition of CRH and related peptides in a dose-dependent manner and blocked by astressin. Our findings suggest the functional expression of CRH-R1 receptor in rat microglia, indicating an important mechanism of interaction between immune and neuroendocrine systems in brain physiological and,pathological conditions. [source] Functions of corticotropin-releasing hormone in anthropoid primates: From brain to placentaAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2006Michael L. Power Corticotropin-releasing hormone (CRH) is an ancient regulatory molecule. The CRH hormone family has at least four ligands, two receptors, and a binding protein. Its well-known role in the hypothalamic-pituitary-adrenal (HPA) axis is only one of many. The expression of CRH and its related peptides is widespread in peripheral tissue, with important functions in the immune system, energy metabolism, and female reproduction. For example, CRH is involved in the implantation of fertilized ova and in maternal tolerance to the fetus. An apparently unique adaptation has evolved in anthropoid primates: placental expression of CRH. Placental CRH stimulates the fetal adrenal zone, an adrenal structure unique to primates, to produce dehydroepiandrosterone sulfate (DHEAS), which is converted to estrogen by the placenta. Cortisol induced from the fetal and maternal adrenal glands by placental CRH induces further placental CRH expression, forming a positive feedback system that results in increasing placental production of estrogen. In humans, abnormally high placental expression of CRH is associated with pregnancy complications (e.g., preterm labor, intrauterine growth restriction (IUGR), and preeclampsia). Within anthropoid primates, there are at least two patterns of placental CRH expression over gestation: monkeys differ from great apes (and humans) by having a midgestational peak in CRH expression. The functional significance of these differences between monkeys and apes is not yet understood, but it supports the hypothesis that placental CRH performs multiple roles during gestation. A clearer understanding of the diversity of patterns of placental CRH expression among anthropoid primates would aid our understanding of its role in human pregnancy. Am. J. Hum. Biol. 18:431,447, 2006. © 2006 Wiley-Liss, Inc. [source] Distribution of corticotropin-releasing hormone in the developing zebrafish brainTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2007Gayathri Chandrasekar Abstract Corticotropin-releasing hormone (CRH) plays a central role in the physiological regulation of the hypothalamus-pituitary-adrenal/interrenal axis mediating endocrine, behavioral, autonomic, and immune responses to stress. Despite the wealth of knowledge about the physiological roles of CRH, the genetic mechanisms by which CRH neurons arise during development are poorly understood. As a first step toward analyzing the molecular and genetic pathways involved in CRH lineage specification, we describe the developmental distribution of CRH neurons in the embryonic zebrafish, a model organism for functional genomics and developmental biology. We searched available zebrafish expressed sequence tag (EST) databases for CRH-like sequences and identified one EST that contained the complete zebrafish CRH open reading frame (ORF). The CRH precursor sequence contained a signal peptide, the CRH peptide, and a cryptic peptide with a conserved sequence motif. RT-PCR analysis showed crh expression in a wide range of adult tissues as well as during embryonic and larval stages. By whole-mount in situ hybridization histochemistry, discrete crh -expressing cell clusters were found in different parts of the embryonic zebrafish brain, including telencephalon, preoptic region, hypothalamus, posterior tuberculum, thalamus, epiphysis, midbrain tegmentum, and rostral hindbrain and in the neural retina. The localization of crh mRNA within the preoptic region is consistent with the central role of CRH in the teleost stress response through activation of the hypothalamic-pituitary-interrenal axis. The widespread distribution of CRH-synthesizing cells outside the preoptic region suggests additional functions of CRH in the embryonic zebrafish brain. J. Comp. Neurol. 505:337,351, 2007. © 2007 Wiley-Liss, Inc. [source] Timing of fetal exposure to stress hormones: Effects on newborn physical and neuromuscular maturationDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2008Lauren M. Ellman Abstract The purpose of the study was to determine the specific periods during pregnancy in which human fetal exposure to stress hormones affects newborn physical and neuromuscular maturation. Blood was collected from 158 women at 15, 19, 25, and 31 weeks' gestation. Levels of placental corticotropin-releasing hormone (CRH) and maternal cortisol were determined from plasma. Newborns were evaluated with the New Ballard Maturation Score. Results indicated that increases in maternal cortisol at 15, 19, and 25 weeks and increases in placental CRH at 31 weeks were significantly associated with decreases in infant maturation among males (even after controlling for length of gestation). Results also suggested that increases in maternal cortisol at 31 weeks were associated with increases in infant maturation among females, although these results were not significant after controlling for length of gestation. Findings suggest that stress hormones have effects on human fetal neurodevelopment that are independent of birth outcome. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 232,241, 2008. [source] Stress, the hippocampus, and epilepsyEPILEPSIA, Issue 4 2009Marian Joëls Summary Stress is among the most frequently self-reported precipitants of seizures in patients with epilepsy. This review considers how important stress mediators like corticotropin-releasing hormone, corticosteroids, and neurosteroids could contribute to this phenomenon. Cellular effects of stress mediators in the rodent hippocampus are highlighted. Overall, corticosterone,with other stress hormones,rapidly enhances CA1/CA3 hippocampal activity shortly after stress. At the same time, corticosterone starts gene-mediated events, which enhance calcium influx several hours later. This later effect serves to normalize activity but also imposes a risk for neuronal injury if and when neurons are concurrently strongly depolarized, for example, during epileptic activity. In the dentate gyrus, stress-induced elevations in corticosteroid level are less effective in changing membrane properties such as calcium influx; here, enhanced inhibitory tone mediated through neurosteroid effects on ,-aminobutyric acid (GABA) receptors might dominate. Under conditions of repetitive stress (e.g., caused from experiencing repetitive and unpredictable seizures) and/or early life stress, hormonal influences on the inhibitory tone, however, are diminished; instead, enhanced calcium influx and increased excitation become more important. In agreement, perinatal stress and elevated steroid levels accelerate epileptogenesis and lower seizure threshold in various animal models for epilepsy. It will be interesting to examine how curtailing the effects of stress in adults, for example, by brief treatment with antiglucocorticoids, may be beneficial to the treatment of epilepsy. [source] Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 geneEPILEPSIA, Issue 3 2008Fernando Díaz-Otero Summary Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; MIM 600513) has been associated with mutations in the genes coding for the alfa-4 (CHRNA4), beta-2 (CHRNB2), and alpha-2 (CHRNA2) subunits of the neuronal nicotinic acetylcholine receptor (nAChR) and for the corticotropin-releasing hormone (CRH). A four-generation ADNFLE family with six affected members was identified. All affected members presented the clinical characteristics of ADNFLE. Interictal awake and sleep EEG recordings showed no epileptiform abnormalities. Ictal video-EEG recordings showed focal seizures with frontal lobe semiology. Mutation analysis of the CHRNB2 gene revealed a c.859G>A transition (Val287Met) within the second transmembrane domain, identical to that previously described in a Scottish ADNFLE family. To our knowledge, this is the third family reported presenting a mutation in CHRNB2. The clinical phenotype appears similar to that described with mutations in CHRNA4, suggesting that mutations in these two subunits lead to similar functional alterations of the nAChR. [source] Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanismEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2002Astrid C. E. Linthorst Summary Serotonin is important for adequate coping with stress. Aberrant serotonin function is implicated in the aetiology of major depression and anxiety disorders. Dysregulation of the hypothalamic,pituitary,adrenocortical axis, involving elevated corticotropin-releasing hormone (CRH) activity, also plays a role in these stress-related illnesses. Here we studied the effects of stress on hippocampal serotonin and the role of the CRH system using in vivo microdialysis. First, rats were subjected to a forced swim stress, resulting in a dramatic increase in hippocampal serotonin (1500% of baseline), which was associated with the occurrence of diving behaviour. The diving-associated increase in serotonin depended on activation of CRH receptors, as it was antagonized by intracerebroventricular pretreatment with D -Phe-CRH12,41. Secondly, the effects of intracerebroventricular administration of CRH and urocortin (0.03,1.0 µg) were studied. Both CRH and urocortin caused a dose-dependent rise in hippocampal serotonin (maximally 350% of baseline) and 5-hydroxyindoleacetic acid levels, suggesting the involvement of CRH receptor type 1. Because the effects of urocortin were prolonged, CRH receptor type 2 could play a role in a later phase of the neurotransmitter response. Experiments using adrenalectomized rats showed that CRH-induced serotonin changes were adrenally independent. These data suggest that the raphe-hippocampal serotonin system is able to mount, CRH receptor-dependent, responses to specific stressful situations that surpass the usually observed maximal increases of about 300% of baseline during stress and enhanced vigilance. [source] Effect of Maternal Nutrient Restriction in Early Gestation on Responses of the Hypothalamic-Pituitary-Adrenal Axis to Acute Isocapnic Hypoxaemia in Late Gestation Fetal SheepEXPERIMENTAL PHYSIOLOGY, Issue 1 2000Paul Hawkins Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic-pituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired O2 fraction (FI,O2). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli. [source] Preclinical Cushing's syndrome: Report of seven cases and a review of the literatureINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2000Masaaki Morioka Abstract Background: Adrenal adenomas showing autonomous cortisol secretion without specific endocrine symptoms are sometimes discovered in patients with adrenal incidentalomas. This entity has been described as subclinical or preclinical Cushing's syndrome (PCS), but the endocrine data of reported cases have varied and the diagnostic criteria of PCS have been uncertain. Methods: We report seven Japanese cases of PCS due to a unilateral, solitary adrenal adenoma with examination of the endocrine data of these patients. The diagnostic parameters of subtle hypercortisolism and the risk of postoperative adrenal insufficiency and surgical indications are discussed and reviewed. Results: In the present cases, the most frequently found biochemical parameters of autonomous cortisol secretion were a low adrenocorticotropic hormone (ACTH) level (100%) and insufficient suppression of cortisol by low-dose dexamethasone (85.7%). Unilateral accumulation of radiopharmaceuticals in tumors was also frequently observed (100%). A postoperative hydrocortisone supplement was given to six of the seven patients for 5,122 days. It was not given to case 4, because a moderate response of 11-deoxycortisol to metyrapone was identified. Plasma ACTH levels and the diurnal rhythm of plasma cortisol rapidly recovered within 3 weeks postoperatively in six of the seven cases. Conclusion: This entity is heterogeneous and various degrees of cortisol excess have been observed. It should be diagnosed in the wide spectrum and the risk of adrenal insufficiency after surgery should be evaluated by dynamic tests such as the corticotropin-releasing hormone (CRH) test. Based on the results of the present study and a review of the literature, PCS patients may not require hydrocortisone supplement therapy for a long period. [source] Maternal Genotype Influences Stress Reactivity of Vasopressin-Deficient Brattleboro RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2003D. Zelena Abstract The role of vasopressin, cosecreted with corticotropin-releasing hormone (CRH), in stress is debated, because both normal as well as reduced adrenocorticotropin hormone (ACTH) rise to an acute challenge has been reported in Brattleboro rats genetically lacking vasopressin (di/di). Because di/di pups could be born either from di/+ (heterozygous) or from di/di mothers, and maternal influence is known to modify adult responsiveness, we investigated whether the influence of maternal genotype could explain the variability. Adult rats from mothers with different genotypes were stressed with 60 min restraint and trunk blood was collected for measuring hormone content by radioimmunoassay at the end of stress. All offspring of di/+ mothers had similar ACTH responses to restraint, while the di/di rats born to, and raised by di/di mothers showed reduced ACTH reactivity to restraint. The di/di rats showed elevated water turnover and required a daily cage cleaning every day, which meant frequent handling. To offset the role of handling, all rats had daily cage cleaning in the next series, but the results were the same as in the first series. To investigate whether lactation, the behaviour of the mother or some other factor during the pregnancy is responsible for the differences, pups from di/+ dams were raised by di/di foster mothers and vice versa. We found that the genotype of parental mother is more important than that of the foster mother. The corticosterone and prolactin elevation normally seen after acute stress was unchanged by family history, maternal or personal genotype. Furthermore, in studies with mutant animals, the rearing conditions should be controlled by the experimenter. In experiments with Brattleboro rats, the use of homozygous and heterozygous rats from the same litters of di/+ dams and di/di males is recommended. Our results suggest that vasopressin is not indispensable for ACTH release, and that the di/di genotype of the parental mother can decrease the stress reactivity of the di/di Brattleboro rats. [source] Hypothalamic-Pituitary-Adrenal Responses to Centrally Administered Orexin-A are Suppressed in Pregnant RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2003P. J. Brunton Abstract Orexins are hypothalamic neuropeptides that stimulate arousal and food intake but also activate the hypothalamic-pituitary-adrenal (HPA) axis. During late pregnancy in the rat, the responsiveness of the HPA axis to stressors is attenuated, and thus we investigated HPA axis responses to centrally administered orexin-A during pregnancy. Intracerebroventricular injection of orexin-A (0.5 µg, 140 pmol) significantly increased plasma adrenocorticotropic hormone and corticosterone concentration within 10 min in virgin female Sprague-Dawley rats, but had no effect in day 21 pregnant rats. Orexin-A significantly increased corticotropin-releasing hormone (CRH) mRNA expression, measured by in situ hybridization, in the paraventricular nucleus (PVN) of the virgin group but not in the pregnant group. Thus, the responsiveness of PVN CRH neurones to orexin-A, and hence the pituitary-adrenal axis, is markedly reduced in pregnancy. This may favour anabolic adaptations in pregnancy. [source] Psychological and Physiological Stress: Impact on Preterm BirthJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 5 2003FAAN professor, Susan Gennaro DSN Stress increases corticotropin-releasing hormone and may ultimately result in increased uterine contractility. Stress also increases cytokine production, which independently may lead to preterm birth or increase susceptibility to infection, thereby increasing the risk of preterm birth. Finally, stress may change health behaviors that lead to preterm birth. Research findings on the relationship between stress and preterm birth have been contradictory. In this article, the authors propose a model of the relationship between stress and preterm birth, evaluate the research on stress and pregnancy outcomes, and discuss the implications for nursing practice and research. [source] Maternal experiences of racism and violence as predictors of preterm birth: rationale and study designPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2001Janet Rich-Edwards Chronic psychological stress may raise the risk of preterm delivery by raising levels of placental corticotropin-releasing hormone (CRH). Women who have been the targets of racism or personal violence may be at particularly high risk of preterm delivery. The aims of this study are to examine the extent to which: (1) maternal experiences of racism or violence in childhood, adulthood, or pregnancy are associated with the risk of preterm birth; (2) CRH levels are prospectively associated with risk of preterm birth; and (3) CRH levels are associated with past and current maternal experiences of racism or violence. We have begun to examine these questions among women enrolled in Project Viva, a Boston-based longitudinal study of 6000 pregnant women and their children. [source] Pattern of maternal circulating CRH in laboratory-housed squirrel and owl monkeysAMERICAN JOURNAL OF PRIMATOLOGY, Issue 11 2010M.L. Power Abstract The anthropoid primate placenta appears to be unique in producing corticotropin-releasing hormone (CRH). Placental CRH is involved in an endocrine circuit key to the production of estrogens during pregnancy. CRH induces cortisol production by the maternal and fetal adrenal glands, leading to further placental CRH production. CRH also stimulates the fetal adrenal glands to produce dehydroepiandrostendione sulfate (DHEAS), which the placenta converts into estrogens. There are at least two patterns of maternal circulating CRH across gestation among anthropoids. Monkeys examined to date (Papio and Callithrix) have an early-to-mid gestational peak of circulating CRH, followed by a steady decline to a plateau level, with a possible rise near parturition. In contrast, humans and great apes have an exponential rise in circulating CRH peaking at parturition. To further document and compare patterns of maternal circulating CRH in anthropoid primates, we collected monthly blood samples from 14 squirrel monkeys (Saimiri boliviensis) and ten owl monkeys (Aotus nancymaae) during pregnancy. CRH immunoreactivity was measured from extracted plasma by using solid-phase radioimmunoassay. Both squirrel and owl monkeys displayed a mid-gestational peak in circulating CRH: days 45,65 of the 152-day gestation for squirrel monkeys (mean±SEM CRH=2,694±276,pg/ml) and days 60,80 of the 133-day gestation for owl monkeys (9,871±974,pg/ml). In squirrel monkeys, circulating CRH declined to 36% of mean peak value by 2 weeks before parturition and then appeared to increase; the best model for circulating CRH over gestation in squirrel monkeys was a cubic function, similar to previous results for baboons and marmosets. In owl monkeys, circulating CRH appeared to reach plateau with no subsequent significant decline approaching parturition, although a cubic function was the best fit. This study provides additional evidence for a mid-gestational peak of maternal circulating CRH in ancestral anthropoids that has been lost in the hominoid lineage. Am. J. Primatol. 72:1004,1012, 2010. © 2010 Wiley-Liss, Inc. [source] Attenuated hypothalamo-pituitary-adrenal axis responses to immune challenge during pregnancy: the neurosteroid,opioid connectionTHE JOURNAL OF PHYSIOLOGY, Issue 2 2008Paula J. Brunton In late pregnancy maternal hypothalamo-pituitary-adrenal (HPA) axis responses to emotional and physical stressors are attenuated. This is expected to minimize the detrimental programming effects of glucocorticoid exposure on the fetuses. We have utilized a model of immune challenge, systemic administration of interleukin-1, (IL-1,), to investigate the underlying mechanisms. Intravenous IL-1, activates corticotropin-releasing hormone (CRH) neurones in the parvocellular division of the paraventricular nucleus (pPVN) via noradrenergic (A2 cell group) neurones in the nucleus tractus solitarii (NTS). Despite comparable activation of these brainstem neurones by IL-1, in virgin and in late pregnant rats, pPVN CRH neurones are activated only in virgin rats. As a consequence IL-1, fails to evoke ACTH and corticosterone secretion in late pregnant rats, in contrast to virgin rats. Suppressed responsiveness of the CRH neurones, and hence the HPA axis, following IL-1, in late pregnancy is explained by presynaptic inhibition of noradrenaline release in the pPVN, due to increased endogenous enkephalin and ,-opioid receptor production in brainstem NTS neurones. The factor that signals to the brain the pregnancy status of the animal and stimulates opioid production in the brainstem is allopregnanolone, a neurosteroid metabolite of progesterone. The supporting evidence for these mechanisms is discussed. [source] Risk Factors and Mechanisms of Preterm Delivery in MalawiAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2004Elizabeth T. Abrams Problem:, We examined risk factors and mechanisms of preterm delivery (PTD) in malaria-exposed pregnant women in Blantyre, Malawi. Method of study:, The human immunodeficiency virus (HIV), malaria, syphilis, and anemia were assessed in a cross-sectional study of 572 pregnant women. In a nested case,control study, chorioamnionitis (CAM) was examined; tumor necrosis factor (TNF)- ,, interleukin (IL)-6, IL-8, macrophage inflammatory protein (MIP)-1,, monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)- ,, cortisol, and corticotropin-releasing hormone were measured in placental, maternal and/or cord blood. Results:, HIV, infrequent antenatal clinic attendance, low-maternal weight, no intermittent preventive malaria therapy (IPT), and CAM were associated with PTD, while malaria was not. Of the 18 compartmental cytokine measurements, elevations in placental and/or cord IL-6 and IL-8 were associated with both CAM and PTD. In contrast, there was no overlap between the cytokines affected by malaria and those associated with PTD. Conclusions:, The HIV and CAM were the major infections associated with PTD in this study. CAM, but not malaria, causes PTD via its effect on proinflammatory cytokines. [source] Reproductive Functions of Corticotropin-Releasing Hormone.AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2004Potential Clinical Utility of Antalarmins (CRH Receptor Type 1 Antagonists), Research Background:, The hypothalamic-pituitary-adrenal (HPA) axis exerts a complex, mostly inhibitory, effect on the female reproductive system. In addition, the principal regulator of this axis, the hypothalamic neuropeptide corticotropin-releasing hormone (CRH) and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, CRH is secreted in peripheral inflammatory sites where it exerts strong inflammatory actions. Antalarmins (CRH receptor type 1 antagonists) have been used to elucidate the roles of CRH in stress, inflammation and reproduction. Method of study:, We review existing data on the effects of CRH in the female reproductive system. Results:, Ovarian CRH participates in female sex steroid production, follicular maturation, ovulation and luteolysis. Uterine CRH participates in decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of parturition. Circulating placental CRH is secreted mostly during the latter half of pregnancy and is responsible for the concurrently increasing physiologic hypercortisolism of this period. After labor and delivery, this hypercortisolism is ensued by a transient suppression of hypothalamic CRH secretion, which may explain the postpartum blues and depression and the increased autoimmune manifestations depression of period, the postpartum period. Conclusions:, These data show that CRH is present in female reproductive tissues, and is regulating key reproductive functions with an inflammatory component, such as ovulation, luteolysis, implantation, and parturition. [source] | |||||||||||||